Slide #1 Antiretroviral Treatment of Adult HIV Infection: 2012 Recommendations of the International...
Transcript of Slide #1 Antiretroviral Treatment of Adult HIV Infection: 2012 Recommendations of the International...
Slide #1
Antiretroviral Treatment of Adult HIV Infection:2012 Recommendations of the
International Antiviral SocietyUSA Panel
Melanie A. Thompson, MD; Judith A. Aberg, MD; Jennifer F. Hoy, MBBS, FRACP; Amalio Telenti, MD, PhD; Constance Benson, MD;
Pedro Cahn, MD, PhD; Joseph J. Eron Jr, MD; Huldrych F. Günthard, MD; Scott M. Hammer, MD; Peter Reiss, MD, PhD;
Douglas D. Richman, MD; Giuliano Rizzardini, MD; David L. Thomas, MD; Donna M. Jacobsen, BS; Paul A. Volberding, MD
The International Antiviral Society–USAThompson et al, JAMA, 2012.
Slide #2
IASUSA Antiretroviral Guidelines1996 – 2012
Slide #3
IASUSA Antiretroviral Guidelines
• Authored by 15-member, international (6 countries) panel
– Members receive no compensation and agree not to participate in industry promotional activities while on the panel
• Evidence-based guidelines are developed by consensus and based upon pathogenesis research, well-designed clinical trials, and large observational cohorts
• Rated on strength of recommendations and quality of evidence
• Primarily for clinicians in highly resourced settings; however, principles are universally applicable
Thompson et al, JAMA, 2012.
Slide #4
Methods
• Systematic literature review of PubMed and EMBASE for data published or presented 7/10 – 5/12
• Hand searches for newly published reports and scientific abstracts, safety reports
• Product efficacy or safety data from ARV manufacturers were reviewed to assure completeness
• Data not published or presented in a peer-reviewed setting were not considered, except safety reports
Thompson et al, JAMA, 2012.
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When to Start Antiretroviral Therapy
Slide #6
Antiretroviral therapy (ART) is recommended and should be offered to all persons with HIV regardless of CD4 cell count.
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Potential Risks and Benefits of Earlier ART Initiation
Potential Benefits
Prevention of progressive immune destruction (AIDS) and improved survival
Decreased immune activation, inflammation, and serious non-AIDS diseases
Decreased drug resistance
Decreased risk for some ARV toxicities
Decreased HIV transmission
Potential Risks
ARV toxicity – short and long term
If adherence is suboptimal, risk of resistance and transmission of resistant virus
Resistance may limit future choices of ART
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Rationale for Recommending ART for All HIV-Infected Adults
• Uncontrolled HIV replication, immune activation and inflammation associated with serious ‘non-AIDS’ illnesses even at CD4 counts > 500/µL– Cardiovascular, hepatic, renal, neurologic, malignancies – High CD4 counts and suppressed virus are associated with
decreased disease incidence
• Newer therapies are more potent, less toxic, more tolerable, and simpler to take leading to improved patient adherence and regimen durability
• ART decreases HIV transmissionThompson et al, JAMA, 2012.
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Earlier ART Associated with Decreased Mortality and Disease Progression:
Observational StudiesStudy Published N Endpoint Relative Hazard P or 95% CI
NA-ACCORD NEJM, 2009 8,362 Death 1.69 CD4 <350 vs 350-500
< 0.001
NA-ACCORD NEJM, 2009 9,155 Death 1.94 CD4 <500 vs > 500
< 0.001
When to Start Consortium
Lancet, 2009 24,444 AIDS or Death
1.28CD4 251-350 vs 351-400
1.04–1.57
HIV-CAUSAL Ann Int Med, 2011
20,971 AIDS or Death
1.38CD4 <350 vs <500
1.23-1.56
CASCADE Arch Int Med, 2011
9,455 Death 0.51 (HR)*CD4 350-499 vs deferred
0.33-0.80
COHERE Plos Med, 2012
75,336 AIDS or Death
0.74 (HR)*CD4 350-<500 on ART
0.96 (HR)*CD4 > 500 on ART
0.58-0.80
0.92-0.99
ATHENA AIDS,2012
3,068 Death, AIDS, Non-AIDS
1.54CD4<200 vs <500
0.33-0.87
Total HIV-1 Transmission Events: 39
HPTN 052: ART Treatment Reduces HIV-1 Transmission
Immediate Arm
4
Delayed Arm
35
p < 0.000196% Reduction with Early ART
Cohen, NEJM 2011; 365:492-505
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When to Start ART: IAS–USA Recommendations 2012
• Patient readiness should be considered when deciding to initiate ART
• ART is recommended and should be offered regardless of CD4 cell count
• The strength of the recommendation and quality of the evidence increases as CD4 count decreases and in the presence of certain conditions
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When to Start ART: IAS–USA Recommendations 2012
• Strength of recommendation and quality of evidence varies– According to CD4 cell count
• CD4 < 500 cells/µL (AIa)
• CD4 > 500 cells/µL (BIII)
– According to clinical condition
• Pregnancy (AIa)
• Chronic HBV (AIIa)
• HCV (may delay until after HCV treatment if CD4 > 500) (CIII)
• Age older than 60 years (BIIa)
• HIV-associated nephropathy (AIIa)
• Acute phase of primary HIV infection, regardless of symptoms (BIII)
Slide #13Initiation of Antiretroviral Therapy in HIV-Infected AdultsCriteria IAS-USA
2012DHHS2012
EACS2011
WHO2010
CD4 count <350/µL
Treat Treat
Treat Treat
CD4 count 350-500/µL
Asymptomatic: ConsiderSymptomatic: Treat
Stage 3 or 4
CD4 count > 500/µL Symptomatic: Treat Stage 3 or 4
Pregnancy Treat Treat Treat < 350/µL;Stage 3-4
History AIDS-defining Illness
Treat Treat Treat Treat
HIV-assoc Nephropathy
Treat Treat Treat Not specified
HBC Coinfection Treat Treat Treat, if HBV tx indicated
Treat, if HBV tx indicated
HCV Coinfection Treat; Consider treating HCV first if CD4 > 500/µL
Treat; Consider treating HCV first if CD4 > 500/µL
Treat if CD4< 500/µL; Defer /consider CD4 >500/µL
Not specified
Age > 60 years Treat Not specified Not specified Not specified
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Other Important New Recommendations
• Early ART initiation when opportunistic infections are present, except cryptococcal meningitis and TB meningitis, where expert consultation is required
• When and how to use existing, new, and emerging therapies
• Monitoring for entry into and retention in care, ART adherence, and quality indicators
• Consideration of PrEP
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Path to an “AIDS-free Generation”
Slide #16• Early diagnosis through increased testing
• Prevention education, condoms, and consideration of PrEP for high-risk HIV uninfected individuals
• Monitor and enhance entry into care and retention in care
• Universal access to ART, for individual and societal benefit
• Monitor and support ART adherence
• Continued efforts at the highest levels to decrease social determinants of health, including stigma
• Continued research on new strategies for treatment, prevention, and cure
• Activism to encourage the political will to fully fund evidence-based prevention and treatment interventions
Slide #17
Backup Slides
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Choice of Initial Regimen
Tenofovir/emtricitabine (TDF/FTC) OR
Abacavir/lamivudine (ABC/3TC)
WITH
Third agent (NNRTI, boosted PI, or InSTI):
• Efavirenz OR
• Atazanavir/r OR
• Darunavir/r OR
• Raltegravir Thompson et al, JAMA, 2012.
HLA B*5701 negativeHIV-1 RNA <100,000 c/mL
HLA B*5701 negativeHIV-1 RNA <100,000 c/mL
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Alternative Initial Antiretroviral Regimens*
Component Alternative Regimens
NNRTI plus nRTIs • Nevirapine plus tenofovir/emtricitabine or abacavir/lamivudine (BIa)
• Rilpivirine/tenofovir/emtricitabine (or rilpivirine plus abacavir/lamivudine) (BIa)
Comment• Severe hepatotoxicity and rash with
nevirapine more common in initial therapy when CD4 cell count is >250/µL in women and >400/µL in men
Thompson et al, JAMA, 2012.
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Alternative Initial Antiretroviral Regimens*
Component Alternative Regimens
PI/r plus nRTIs • Darunavir/r plus abacavir/lamivudine (BIII)
• Lopinavir/r plus tenofovir/emtricitabine (BIa) (or abacavir/lamivudine) (BIa)
Comment• Other alternative PIs include
fosamprenavir/r and saquinavir/r but indications to use these options for initial treatment are rare.
Thompson et al, JAMA, 2012.
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Alternative Initial Antiretroviral Regimens*
Component Alternative Regimens
InSTI plus nRTIs • Raltegravir plus abacavir/lamivudine (BIIa)
• Elvitegravir/cobicistat/tenofovir/emtricitabine** (BIb)
Comment• Raltegravir is given twice daily;
experience with elvitegravir/cobicistat/tenofovir/emtricitabine is limited to 48-week data.
* Submitted for regulatory approval Thompson et al, JAMA, 2012.
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CCR5 AntagonistBased and nRTI-Sparing Initial Regimens in Special Circumstances Only
Component Regimens
CCR5 antagonist plus nRTIs, (NNRTI-, PI-, and InSTI-sparing)
PI/r plus InSTI (nRTI-sparing)
• Maraviroc plus tenofovir/emtricitabine or abacavir/lamivudine (CIII)
• Darunavir/r plus raltegravir (BIIa)• Lopinavir/r plus raltegravir (BIa)
Thompson et al, JAMA, 2012.* See comments